ELAPRASE + Prophylactic Therapy for Hunter Syndrome

Recruiting at 10 trial locations

Overseen By Takeda Contact

Age: < 18

Sex: Male

Trial Phase: Phase 4

Sponsor: Takeda

Must be taking: Elaprase

Must not be taking: Growth hormones

Disqualifiers: Investigational drug, Growth hormones, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

5 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special treatment plan can prevent or reduce the body's reaction against ELAPRASE in young boys with Hunter syndrome. ELAPRASE treats Hunter syndrome, a rare genetic condition affecting growth and development. Participants will receive ELAPRASE along with other medicines designed to help the body accept the treatment better. Boys under six years old, who are new to ELAPRASE treatment and have a confirmed diagnosis of Hunter syndrome, might be suitable for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it excludes participants who are currently using any medication that could affect the study. It's best to discuss your current medications with the study team to see if they might impact your eligibility.

What is the safety track record for these treatments?

A previous study found ELAPRASE to be generally safe for treating Hunter syndrome. However, some patients experienced serious allergic reactions, including anaphylaxis, a severe allergic response that can occur during or after treatment. Therefore, monitoring patients closely during and after each infusion is important.

The prophylactic immune tolerizing regimen (ITR) in this study includes rituximab, methotrexate, and IVIG. Rituximab, when combined with IVIG, has been studied for safety in other conditions and is generally considered safe. However, fewer studies have specifically examined this combination, so some risks may not be fully understood.

In summary, ELAPRASE and the ITR have shown some safety in past studies. However, like any treatment, they may have side effects that require careful monitoring. Always consult a doctor about any concerns or questions. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this treatment for Hunter Syndrome because it combines ELAPRASE with a prophylactic therapy consisting of rituximab, methotrexate, and IVIG. Unlike standard enzyme replacement therapies, this approach aims to reduce immune system reactions that can limit the effectiveness of treatment by managing anti-idursulfase antibody levels. Additionally, ELAPRASE is dosed based on the participant's weight and administered weekly, ensuring a tailored and consistent delivery that could enhance its efficacy over time. This combination strategy could offer a more robust and personalized treatment option for patients with Hunter Syndrome, addressing some limitations of current therapies.

What is the effectiveness track record for ELAPRASE in treating Hunter syndrome?

Research has shown that ELAPRASE effectively treats Hunter syndrome. It improves walking, lowers certain substances in the urine, and reduces liver and spleen size. Studies also indicate that long-term use enhances breathing and overall health.

In this trial, participants will receive a prophylactic immune tolerizing regimen (ITR) to help the body accept ELAPRASE more easily by reducing immune reactions. Early findings suggest that a combination of rituximab, methotrexate, and intravenous immunoglobulin (IVIG) can help the body tolerate treatments like ELAPRASE. This approach may improve treatment outcomes by preventing the body from rejecting the therapy. ^{2 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for treatment-naïve boys under 6 with Hunter syndrome, having specific enzyme deficiencies and gene mutations. They must not have used ELAPRASE or certain other treatments recently and should be able to follow the study protocol without any medical conditions that could interfere.

Inclusion Criteria

I have been diagnosed with MPS II.

Your enzyme activity levels for certain substances in your body are within the normal range.

You do not have antibodies against the drug idursulfase in your blood.

Exclusion Criteria

Within 30 days prior to the first dose of investigational product, the participant has been enrolled in a clinical study that may impact this study

I am not on any medication that could interfere with the study.

Participant has received treatment with any investigational drug within the 30 days prior to study entry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive ELAPRASE treatment and a prophylactic immune tolerizing regimen (ITR) for up to 104 weeks. The ITR includes Rituximab, Methotrexate, and IVIG in a 5-week cycle.

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ELAPRASE
• Intravenous Immunoglobulin (IVIG)
• Methotrexate
• Rituximab

Trial Overview The study tests if a preventive immune regimen can stop or lessen high titer anti-idursulfase antibodies in patients taking ELAPRASE. It includes Rituximab, Methotrexate, IVIG alongside ELAPRASE over up to 104 weeks with assessments every six months.

How Is the Trial Designed?

Group I: ITR + ELAPRASE Experimental Treatment 4 Interventions

Participants will receive prophylactic ITR which consist of rituximab, methotrexate and IVIG in a 5-week cycle. Following the completion of 1 cycle and at the Month 6, 12, and 18 study visits, an assessment will be made regarding the need for administering another 5-week cycle of the ITR depending on the trend of the participants anti-idursulfase antibody titers and lymphocyte quantitation and CD19 percent (%) recovery. Elaprase treatment (IV, weekly) will start 1 day after the initiation of the first cycle of ITR and continue for 104 weeks. The dose of ELAPRASE will be calculated based on the participant's weight at each visit.

ELAPRASE is already approved in United States for the following indications:

Approved in United States as ELAPRASE for:

• Hunter syndrome (Mucopolysaccharidosis II, MPS II)

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Published Research Related to This Trial

Enzyme replacement therapy (ERT) with idursulfase shows beneficial effects in young children under 5 years with Hunter syndrome, including reduced urinary GAG levels and stabilization or improvement in joint mobility after 6 to 14 months of treatment.

The treatment also helped maintain normal height growth and reduced organ size in some patients, suggesting that ERT is effective and safe for this age group, although more studies are needed for direct comparisons with older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS). Alcalde-Martín, C., Muro-Tudelilla, JM., Cancho-Candela, R., et al.[2022]

In a study involving 28 boys aged 1.4 to 7.5 years with Hunter syndrome, idursulfase was found to be generally safe, with most adverse events being mild or moderate, although 57% reported treatment-related adverse events.

Idursulfase treatment led to a decrease in organ size and urinary glycosaminoglycan levels, indicating potential efficacy, while growth rates and developmental quotients remained stable, similar to outcomes seen in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label study evaluating safety and clinical outcomes in children (1.4-7.5 years) with Hunter syndrome receiving idursulfase enzyme replacement therapy. Giugliani, R., Hwu, WL., Tylki-Szymanska, A., et al.[2022]

Enzyme replacement therapy (ERT) with idursulfase beta has been shown to be effective and well-tolerated in a 13-year-old patient with attenuated MPS II, especially after experiencing adverse reactions to idursulfase.

Both idursulfase and idursulfase beta are approved treatments for MPS II, but idursulfase beta may offer a safer alternative for patients who develop infusion-related reactions to idursulfase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report of treatment experience with idursulfase beta (Hunterase) in an adolescent patient with MPS II. Ngu, LH., Ong Peitee, W., Leong, HY., et al.[2022]

In a study of 124 patients with Hunter syndrome who started enzyme replacement therapy with idursulfase before the age of 6, treatment was found to be safe, with no new safety concerns identified, despite 26.6% experiencing infusion-related reactions.

The therapy demonstrated effectiveness, as evidenced by a significant reduction in urine glycosaminoglycan levels and liver size after at least 6 months of treatment, indicating clinical benefits for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idursulfase treatment of Hunter syndrome in children younger than 6 years: results from the Hunter Outcome Survey. Muenzer, J., Beck, M., Giugliani, R., et al.[2022]

Idursulfase (Elaprase) is the first approved enzyme replacement therapy for Hunter syndrome, showing significant benefits in a phase II/III clinical trial, including increased walking distance, improved pulmonary function, and reduced organ size and urinary glycosaminoglycans (GAGs) excretion in patients.

The treatment is generally well tolerated, although some patients may experience infusion reactions, marking idursulfase as a promising symptomatic therapy that addresses the underlying enzymatic deficiency in Hunter syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idursulfase in Hunter syndrome treatment. Zareba, G.[2017]

Long-term enzyme replacement therapy with idursulfase for Hunter syndrome showed sustained clinical improvements over 3 years, including a 25.1% increase in absolute forced vital capacity and significant enhancements in walking distance.

While 53% of patients experienced infusion-related adverse events, these decreased over time, and the presence of neutralizing antibodies in 23% of patients was associated with reduced pulmonary function improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. Muenzer, J., Beck, M., Eng, CM., et al.[2022]

Enzyme replacement therapy (ERT) with idursulfase for Hunter syndrome has shown positive effects in patients of all ages, including improvements in weight, height, and a significant reduction in glycosaminoglycan (GAG) levels, which are associated with the disease.

The therapy led to notable clinical improvements, such as recovery from carpal tunnel syndrome and decreased organomegaly, particularly in one patient who experienced an 86% reduction in GAGs, highlighting the efficacy of ERT in managing symptoms and preventing disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome. Dalmau Serra, J., Vitoria Miñana, I., Calderón Fernández, R., et al.[2015]

In a study of 32 Korean patients with Hunter syndrome receiving enzyme replacement therapy (ERT) for at least 2 years, significant growth improvements were observed, particularly in younger patients starting treatment before age 6.

The study indicated that ERT may have a reduced effect on growth in older patients, especially those with more severe forms of Hunter syndrome, suggesting that early intervention could be crucial for better growth outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of enzyme replacement therapy on linear growth in Korean patients with mucopolysaccharidosis type II (Hunter syndrome). Cho, SY., Huh, R., Chang, MS., et al.[2021]

The study developed specific polyclonal antibodies against human iduronate 2-sulphate sulphatase (IDS), which can be used to detect and quantify IDS in fermentation extracts from Pichia pastoris and Escherichia coli, crucial for enzyme replacement therapy in Hunter syndrome.

These antibodies are effective in distinguishing IDS from other proteins, allowing for their application in both an ELISA system for quantification and in affinity chromatography for purification, enhancing the potential for developing effective treatments for Hunter syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Production of polyclonal antibodies to protein iduronate-2-sulphate sulphatase (IDS) and development of a detection system for human recombinant IDS]. Peña, O., Sosa, A., Echeverri, O., et al.[2007]

Citations

1. elaprase.com elaprase.com/hcp/clinical-trial/

Clinical trial outcomes In the pivotal trial, ELAPRASE achieved the primary endpoint, improved walking capacity, reduced urinary GAG levels, and reduced liver and spleen volume in ...

2. elaprase.com elaprase.com/getting-started-support/hunter-outcome-survey/

ELAPRASE®| Hunter Outcome Survey ELAPRASE has been shown to improve walking ability in patients 5 yrs and older. In patients 16 months to 5 yrs old, ELAPRASE did not show improvement in disease ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5627440/

3-year data from the hunter outcome survey (HOS) - PMC These findings suggest that idursulfase has a positive effect on uGAG levels, 6MWT results, LVMI, FVC, FEV 1 and hepatosplenomegaly after 1, 2 and 3 years ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1098360025001078

Efficacy and safety of idursulfase beta in the treatment ... Conclusion. Idursulfase beta is a safe and effective treatment option in mucopolysaccharidosis II, addressing crucial somatic ailments presented by patients.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05494593

NCT05494593 | A Study of ELAPRASE in Treatment-naïve ... The main aim of this study is to evaluate the ability of a prophylactic immune tolerizing regimen (ITR) to prevent or reduce the development of high titer ...

6. elaprase.com elaprase.com/what-is-elaprase/risk-and-safety/

ELAPRASE® Risk & Safety Profile Some patients have experienced serious allergic reactions, including anaphylactic reactions, during and up to 24 hours after an ELAPRASE infusion.

7. elaprase.com elaprase.com/Content/pdf/resource-pdf/hcp/ELAPRASE%20ISI.pdf

Indications and Usage The safety and efficacy of ELAPRASE have not been established in pediatric patients less than 16 months of age. Important Safety Information. •.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32342708/

Safety and efficacy of idursulfase in the treatment ... Conclusion: Long-term idursulfase treatment was well tolerated, and effective in improving clinical features, reducing urinary UA, and slowing disease ...

9. elaprase.com elaprase.com/hcp/about/safety-information/

ELAPRASE safety results See Important Safety Information including Boxed Warning for lifethreatening anaphylactic reactions, indications, adverse reactions, and immunogenicity.